Revisiting the Conformational Equilibrium of 1,1,2-Trifluoroethane and 1,1,2,2-Tetrafluoroethane: An NBO Study.

Organofluorine compounds are key to pharmaceutical, agrochemical, and high-performance material applications, where C-F bond conformations influence critical properties such as solubility, lipophilicity, and biological activity. While the conformational behavior of 1,2-difluoroethane and its characteristic effect is well understood, the structural preferences of 1,1,2-trifluoroethane and 1,1,2,2-tetrafluoroethane have remained less explored, particularly in light of hyperconjugation theory. In this quantum-chemical study, the conformational equilibria of these two model fluoroalkanes were investigated using density functional theory and Natural Bond Orbital (NBO) analysis, with complementary NMR coupling constant calculations. The results reveal that Lewis-type interactions govern conformational stability, favoring the conformer in 1,1,2-trifluoroethane and the conformer in 1,1,2,2-tetrafluoroethane. Nevertheless, electron delocalization plays an essential role in ensuring that staggered conformations remain energy minima, as fully localized electronic structures would yield only a single conformer for each compound. These findings refine our understanding of hyperconjugative and electrostatic effects in fluorinated ethanes and provide a more nuanced framework for predicting conformational preferences in difluoromethyl-containing systems.